Does tyrosine kinase modulate delayed-rectifier K channels in guinea pig ventricular cells?
Phosphorylation by tyrosine kinases has been shown to promote cellular growth and hypertrophy and to play a key role in modulating ion channels. We have examined possible effects of genistein, a protein tyrosine kinase (PTK) inhibitor, on cardiac delayed-rectifier K currents (IK). Guinea pig ventricular myocytes were voltage-clamped by conventional whole-cell mode (5.4 mM [K]out/150 mM [K]in; pCa = 8; 36 degrees C). Amplitudes of tail and steady-state (2-s pulse) currents were measured as IK. Micromolar concentrations of genistein (10-100 microM) reversibly inhibited basal, swelling-enhanced (by 70% hypotonic solution), and intrapipette Cyclic adenosine monophosphate (cAMP) (1 mM)-enhanced IK concentration-dependently, while intrapipette cAMP-enhanced IK were also affected by daidzein, an inactive analog of genistein. In contrast, lavendustin A (10 microM) and tyrphostin 51 (100 microM), other types of PTK inhibitors, had no effect on IK. These results suggest that genistein may inhibit IK and that this inhibition is not mediated by an inhibition of tyrosine kinase activity.
Washizuka
T
T
Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine, Japan.
Horie
M
M
Obayashi
K
K
Sasayama
S
S
D000818:Animals; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019833:Genistein / Q000494:pharmacology; D006168:Guinea Pigs; D006352:Heart Ventricles / Q000166:cytology*; D009206:Myocardium / Q000166:cytology; D018408:Patch-Clamp Techniques; D010636:Phenols / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000502:physiology*
D004791:Enzyme Inhibitors; D010636:Phenols; D015221:Potassium Channels; C062898:lavendustin A; D019833:Genistein; D011505:Protein-Tyrosine Kinases